Study to Evaluate Imetelstat (JNJ-63935937) in Subjects With International Prognostic Scoring System (IPSS) Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

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The purpose of this study is to evaluate the efficacy and safety of imetelstat in transfusion dependent participants with low or intermediate-1 risk myelodysplastic syndrome (MDS) that is relapsed/refractory to erythropoiesis-stimulating agent (ESA) treatment.

Condition or disease

Intervention/treatment

Phase

Myelodysplastic Syndromes

Drug: ImetelstatDrug: Placebo

Phase 3

Detailed Description:

This is a Phase 2/3, multicenter study of imetelstat that consists of 2 parts. Part 1 is an open‐label, single-arm design to assess the efficacy and safety of imetelstat. Approximately 55 participants will be enrolled in Part 1, including the expansion cohort, and be followed-up for safety, hematologic improvement and reduction in transfusion requirement. Part 2 of the study will be initiated if data from Part 1 are supportive of a satisfactory benefit/risk profile. Part 2 is a double‐blind, randomized design to compare the efficacy of imetelstat with placebo. Approximately 170 eligible participants will be randomized in a 2:1 ratio to receive either imetelstat or placebo, respectively. Each part of the study will consist of 3 phases: a Screening phase (up to 28 days); a treatment phase; and a post-treatment follow-up phase which will continue until death, lost to follow-up, withdrawal of consent, or the End of the Study (whichever occurs first). The End of the Study is defined as 2 years after the study entry of the last participant or anytime the sponsor terminates the study, whichever comes first.

Imetelstat will be administered at a starting dose of 7.5 milligram per kilogram (mg/kg) given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.

Drug: Imetelstat

Imetelstat will be administered at a starting dose of 7.5 milligram per kilogram (mg/kg) given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.

Experimental: Part 2: Imetelstat

Imetelstat will be administered at a starting dose of 7.5 milligram per kilogram (mg/kg) given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.

Drug: Imetelstat

Imetelstat will be administered at a starting dose of 7.5 milligram per kilogram (mg/kg) given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.

Progression free survival will be assessed as the time interval from study Day 1 to the first date of disease progression or death from any cause, whichever occurs first. As per IWG criteria disease progression is defined as: at least one of the following: at least 50 percent (%) decrement from maximum response levels in granulocytes or platelets; reduction in hemoglobin by greater than or equal to (>=) 1.5 gram per deciliter (g/dL); transfusion dependence.

Time to Progression to Acute Myeloid Leukemia [ Time Frame: During study (approximately 2 years) ]

Assessment of Quality of Life in Myelodysplasia Scale (QUALMS) in Part 2 [ Time Frame: During study (approximately 2 years) ]

The QUALMS is a 38-item measure that assesses health-related quality of life for patients with MDS. Thirty-three items are used to calculate the total score, as well as the 14 item physical burden (QUALMS-P), 3-item benefit-finding (QUALMS-BF), and 11-item emotional burden (QUALMS-E) subscales.

Assessment of Participant Global Impression of Change (PGIC) in Part 2 [ Time Frame: During study (approximately 2 years) ]

The Participant Global Impression of Change (PGIC) is a single-item questionnaire designed to provide an overall assessment of treatment from the participant's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of "very much improved" or "much improved".

Change From Baseline in QTc Interval at Day 1 of Part 2 [ Time Frame: Baseline and Day 1 ]

Change from baseline in QTc interval by Fridericia's correction method (ΔQTcF) will be assessed in part 2.

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Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Man or woman greater than or equal to (>=) 18 years of age

In Part 1, diagnosis of myelodysplastic syndrome (MDS) according to World Health Organization (WHO) criteria

Red blood cell (RBC) transfusion dependent, defined as requiring at least 4 RBC units transfused over an 8-week period during the 16 weeks prior to Study Entry; pre-transfusion hemoglobin (Hb) should be less than or equal to 9.0 gram per deciliter (g/dL) to count towards the 4 units total